Methylation, Choline, and MTHFD1 Gene

Written by Joe Cohen, BS | Last updated:

Methylfolate and Vitamin B12 are not always the answer for an undermethylator.

The general thought process is:

Bad MTHFR gene → undermethylator → methylfolate and B12.

While MTHFR does play a significant role in methylation, there are other genes that need to be looked at, and other compounds that might benefit you even more.

Like the MTHFD1 gene and choline.

How MTHFD1 Impacts Methylation

The MTHFD1 gene codes for an enzyme that metabolizes tetrahydrofolate and enables the process of methylation.

Vitamin B9 or folic acid needs to be “activated” for L-methylfolate to achieve its health effects.

And the MTHFD1 enzymes play vital roles in this process.

Folate and choline impact the complex cycle of methylation reactions, as they both supply methyl groups for the production of methionine from homocysteine.

MTHFD1 participates in this cycle by creating methyl-THF.

This is why choline intake is extremely important and depends on MTHFD1 activity.

Our latest SNPit episode actually dives more into the science behind the MTHFD1 (listen here on Spotify or Apple).

What A Negative MTHFD1 Variant Means

How exactly does choline supply methyl groups?

Choline is a precursor to a molecule called betaine, which plays a significant role in the methylation cycle.

Reduced MTHFD1 activity means less methyl-THF, which forces the body to use more choline for methylation.

I carry the negative variant that decreases my gene expression.

Because of this, if your intake of choline is low, this effect may become even more significant and contribute to the signs of deficiency.

Which, in return, results in heart health problems, mental health issues, fertility problems, birth defects, and more.

The Importance of MTHFD1 and Other Genes

MTHFR and MTHFD1 aren’t the only genes responsible for methylation. We also have MTR and MTRR, as well as PEMT, and many others.

If you do carry the negative variant and you look at it in isolation, then choline is probably the best supplement that you can take to improve your methylation.

But because there are other genes that impact methylation, it’d be inaccurate to do that.

Even with MTHFR, which plays a more significant role in methylation, you can’t just look at individually.

Which is why it’s important to understand the full picture of your DNA, and why we’ve built SelfDecode.

We’re the only company in the world that analyzes all of your genes related to methylation to give you a risk score on your predisposition to undermethylating, as well as personalized recommendations to optimize your methylation.


About the Author

Joe Cohen, BS

Joe Cohen, BS

Joe Cohen flipped the script on conventional and alternative medicine…and it worked. Growing up, he suffered from inflammation, brain fog, fatigue, digestive problems, insomnia, anxiety, and other issues that were poorly understood in traditional healthcare. Frustrated by the lack of good information and tools, Joe decided to embark on a learning journey to decode his DNA and track his biomarkers in search of better health. Through this personalized approach, he discovered his genetic weaknesses and was able to optimize his health 10X better than he ever thought was possible. Based on his own health success, he went on to found SelfDecode, the world’s first direct-to-consumer DNA analyzer & precision health tool that utilizes AI-driven polygenic risk scoring to produce accurate insights and health recommendations. Today, SelfDecode has helped over 100,000 people understand how to get healthier using their DNA and labs.
Joe is a thriving entrepreneur, with a mission of empowering people to take advantage of the precision health revolution and uncover insights from their DNA and biomarkers so that we can all feel great all of the time.


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